Galactosemia: what is it, causes, symptoms, treatment, prognosis

What is galactosemia?

Galactosemia Is a rare hereditary disorder of carbohydrate metabolism that affects the body's ability convert galactose (sugar found in milk, including mother's milk) to glucose (another type Sahara). The disorder results from a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT), which is vital for this process.

Early diagnosis and treatment using a lactose-restricted (dairy-free) diet absolutely necessary to avoid profound mental retardation, liver failure and death during the period newborns. Galactosemia is inherited as an autosomal recessive genetic disorder. Classic galactosemia and clinical variant galactosemia can lead to life-threatening health problems if treatment is not started soon after the baby is born.

Signs and symptoms

An infant with galactosemia appears normal at birth, but after a few days or weeks loses appetite

 (anorexia) and begins to vomit excessively. Yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), enlargement of the liver (hepatomegaly), the appearance of amino acids and protein in the urine, impaired growth and, ultimately, the accumulation of fluid in the abdominal cavity (ascites) with abdominal edema. Diarrhea, irritability, lethargy, and bacterial infection can also be early signs of galactosemia. Over time, depletion of body tissues, severe weakness and extreme weight loss occurs if lactose is not removed from the diet.

Children with galactosemia who are untreated early may show physical and mental retardation and are particularly susceptible to cataract in infancy or childhood. In severe cases, overwhelming neonatal infection can lead to life-threatening complications, but in mild cases the signs are mild and there are no major impairments.

To avoid the effects of galactosemia, which may include liver failure and kidney dysfunction, brain damage and / or cataracts, children should be treated promptly by removing lactose from the diet. Children who are treated with this special diet usually show satisfactory general health and growth. They can make reasonable, albeit often sub-optimal, intellectual progress. Speech and learning problems, as well as some behavioral problems, can still arise. Ovarian dysfunction is almost always observed in girls with classic galactosemia and is associated with an increase in blood levels of the hormone gonadotropin, follicle-stimulating hormone (FSH); men with galactosemia usually do not have abnormalities in the function of the gonads.

The aforementioned complications associated with the classical and clinical variant of galactosemia did not occur in people with galactosemia of the Duarte variant, which is the best example of a biochemical variant galactosemia. However, a minority of subjects experienced developmental delays and / or speech impairments, but it is unclear if this is due to accumulation of galactose and its metabolites. Persons with galactosemia Duarte do not need special nutrition.

Causes

Galactosemia occurs due to abnormalities or changes (mutations) in a gene GALT, which leads to a deficiency of the enzyme galactose-1-phosphate-uridyltransferase (GALT). This leads to an abnormal accumulation of galactose-related chemicals in various organs of the body, causing the symptoms and physical signs of galactosemia.

The enzyme galactose-1-phosphate uridyltransferase (GALT) is required for the breakdown of milk sugar, galactose. A deficiency of this enzyme leads to the accumulation of toxic products: galactose-1-phosphate (a derivative of galactose) and galactitol (an alcoholic derivative of galactose). Galactitol accumulates in the lens of the eye, where it causes lens edema and protein deposition, followed by cataracts. Accumulation of galactose-1-phosphate is thought to cause other signs and symptoms of the disease.

Galactosemia is an autosomal recessive genetic disorder. Recessive genetic disorders occur when a person inherits a non-working gene from each parent. If a person receives one working gene and one non-working gene for a disease, the person will be a carrier of the disease, but usually not asymptomatic. The risk for two carrier parents passing on both non-working genes and therefore conceiving a sick child is 25% with each pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The probability for a child to receive working genes from both parents is 25%. The risk is the same for men and women.

Affected populations

The classic form of the disease is diagnosed in the range from 1 / 16,000 to 1 / 48,000 births using programs screening of newborns around the world, depending on the diagnostic criteria used by the program. Violation was reported across all ethnic groups. An increased incidence of galactosemia is observed in persons of Irish descent. The clinical variant of galactosemia is most common in African Americans and Indigenous Africans in South Africa who have a specific mutation in the GALT gene.

Symptomatic disorders

Symptoms of the following disorders may be similar to those of galactosemia. Comparisons can be useful for differential diagnosis:

• Galactokinase deficiency (GALK) is associated with cataracts, increased blood galactose concentration, and increased urinary galactitol concentration. Galactitol accumulates in the lens of the eye, where it causes lens edema and protein deposition, followed by cataracts. GALK deficiency is an autosomal recessive genetic disorder caused by mutations in the gene GALK1 and is diagnosed by a decreased activity of the GALK enzyme.
• Uridine diphosphate-galactose-4-epimerase deficiency (GALE) is similar to GALT deficiency when it appears during the neonatal period. Severe was reported in only 8 patients. GALE deficiency is an autosomal recessive genetic disorder caused by mutations in the gene GALE and is diagnosed by a decreased activity of the GALE enzyme.
• Lactose intolerance (or hypolactasia) is a metabolic disorder characterized by an inability to break down lactose, the predominant sugar in milk and dairy products. People with hypolactasis cannot properly digest lactose because they lack an intestinal enzyme, lactase, which is the key to lactose digestion. Lactose is a complex sugar made up of two different sugar molecules (disaccharide), galactose and glucose, each of which is a simple (monosaccharide) sugar and is more easily absorbed in the intestines of the body and processed into others organs. People with lactase deficiency experience seizures, nausea, bloating, stomach rumbling, gas and / or diarrhea after eating or consuming lactose-rich foods, not all of which are dairy products. The symptoms are more serious when they occur in a newborn baby.
• Neonatal hepatitis Is a general term used to refer to liver damage that occurs shortly before and / or after birth. Neonatal hepatitis can be caused by viruses, metabolic or genetic disorders, or other rare diseases that affect or impair liver function. In some children, the cause of liver damage is unknown - these cases are called idiopathic neonatal hepatitis (INH). The signs of idiopathic neonatal hepatitis can vary significantly from one person to the next. Often there are signs common to liver diseasesincluding yellowing of the sclera of the eyes and skin (jaundice), enlarged liver (hepatomegaly), and unusually dark urine. Most people with idiopathic neonatal hepatitis recover completely from the disease; However, in some, the disease progresses to chronic liver disease.

Diagnostics

Galactosemia can be detected with a blood test. This test is performed as part of a standard newborn screening test. Before conception, adults who have a relative or child with the disorder may be tested to see if they carry the gene that causes the disorder. The risk of developing the disease in a child whose both parents are carriers of the gene is 1 in 4. Carriers are people who have the abnormal gene responsible for a particular disease but have no symptoms or visible signs of the disease.

Another test is done to check for elevated levels of galactose in the urine.

Standard treatments

Infants and children with galactosemia should eat a lactose-restricted (dairy-free) diet. products) containing lactose-free milk replacers and other products such as soy products beans.

The lactose tolerance test should NOT be given to children with galactosemia. Fortunately, an infant with galactosemia can synthesize galactolipids and other essential galactose-containing compounds without the presence of galactose in food. Therefore, satisfactory physical development is largely possible with a strict diet.

Speech therapy may be necessary for children with childhood speech apraxia or dysarthria. For school-aged children, some individuals may require individualized learning plans and / or professional learning assistance, depending on the psychological development assessment. Hormone replacement therapy can also be used in cases of delayed puberty, and then in adolescence for a secondary loss of menstrual periods called premature ovarian failure (PNI).

Appropriate treatment (such as antibiotics) can be used to control infection during the neonatal period. The emotional impacts of a strict diet may require attention and supportive measures throughout childhood. Genetic counseling is recommended for families with children who have galactosemia.

Many people need to take calcium and vitamin supplements.

Forecast

If galactosemia is detected at birth and treated appropriately, liver and kidney problems do not develop and initial intellectual development remains normal. However, even with adequate therapy, children with galactosemia may have a lower IQ (IQ) than their siblings, and during adolescence they often develop speech and balance. Many children also have cataracts. Girls often have ovaries that do not function, and only a few are able to become pregnant naturally. In boys, testicular function is not impaired.